PB2307: PHARMACOKINETICS, EFFICACY AND SAFETY OF SUBCUTANEOUS VERSUS INTRAVENOUS RITUXIMAB COMBINED WITH CHOP IN CHINESE PATIENTS WITH UNTREATED CD20-POSITIVE DIFFUSE LARGE B CELL LYMPHOMA: A RANDOMIZED TRIAL
Authors: Yan Gao, Liling Zhang, Sujun Gao, Yu Yang, Qing-Yuan Zhang, Huilai Zhang, Pengcheng He, Fei LI, Hongmei Jing, Susan Grange, Lilian Bu, Qianming Wang, Yanjie Wang, Huiqiang Huang
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin’s lymphoma (NHL) in China, accounting for approximately 54% of B-cell origin NHL cases. The standard of care for DLBCL is eight cycles of intravenous (IV) rituximab combined with six or eight cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Since March 2014, rituximab has also been available as a solution for subcutaneous (SC) injection in various countries. Compared with IV administration, SC administration of rituximab is shorter, less invasive, and reduces the treatment burden for patients. Global trials demonstrated that SC rituximab at a fixed dose of 1400 mg had non-inferior rituximab serum levels, and comparable efficacy and safety to IV rituximab 375 mg/m2 in NHL patients; however, data in Chinese patients are lacking. Aims: This study evaluated the pharmacokinetics (PK), efficacy and safety of SC versus IV rituximab, both in combination with CHOP, in previously untreated patients with CD20-positive (CD20+) DLBCL in China (NCT04660799). Methods: This was a Phase II, randomized, controlled, open-label study conducted in nine centers in China between 24 February 2021 and 23 May 2022. Patients aged between 18–80 (n=50) years with untreated CD20+ DLBCL were randomized 1:1 to the following dosing regimens: one cycle of IV rituximab plus seven cycles of SC rituximab (RSC-CHOP), or eight cycles of IV rituximab (RIV-CHOP), both in combination with six or eight cycles of CHOP every 3 weeks. IV and SC rituximab were administered at 375 mg/m2 and 1400 mg doses, respectively. Eligible patients were stratified during randomization according to International Prognostic Index (IPI) scores (IPI 0–2 versus IPI 3–5). The primary endpoint was the ratio of trough rituximab serum concentration of SC rituximab to IV rituximab (Ctrough,SC/Ctrough,IV) at Cycle 7. Non-inferiority of Ctrough,SC versus Ctrough,IV was shown if the lower limit of the two-sided 90% confidence interval (CI) exceeded 0.80. Complete response rate (CRR) was determined using Lugano Response Criteria for Malignant Lymphoma, reviewed by an Independent Review Committee (IRC). Other PK and efficacy endpoints, as well as safety, tolerability, and immunogenicity were also evaluated. Results: Fifty patients were enrolled in this study: 26 received RSC-CHOP and 24 received RIV-CHOP; median age was 61.5 (range 19–79) years. The baseline stratification characteristics of IPI scores were well balanced between the two treatment arms; 21 (42.0%) patients had an IPI score of 3–5. The majority of patients in both SC (24/26, 92.3%) and IV (19/24, 79.2%) rituximab arms completed all eight cycles of rituximab. Geometric mean ratio of Ctrough,SC/Ctrough,IV at Cycle 7 was 1.52 (90% CI: 1.28–1.79), demonstrating non-inferiority for SC rituximab compared with IV rituximab. The IRC-assessed CRR in the SC rituximab arm (80.8%; 95% CI: 60.7–93.5) was similar to the IV rituximab arm (62.5%; 95% CI: 40.6–81.2). The safety profile was similar in both arms. There were no new safety findings, and the incidence of adverse events was comparable between treatment arms, in line with data from previous global studies on SC rituximab. Summary/Conclusion: SC rituximab demonstrated non-inferior rituximab serum trough levels, as well as comparable efficacy and tolerability to IV rituximab in Chinese patients with previously untreated CD20+ DLBCL, indicating that SC rituximab is a viable route of administration, with potential to reduce burden of administration for healthcare professionals and patients. Keywords: Non-Hodgkin’s lymphoma, Diffuse large B cell lymphoma, Rituximab, DLBCL